1. Field of the Invention
This invention relates to methods of treating cancers or tumors with a delta-like ligand 4 (Dll4) antagonist, in particular, human antibodies or fragments thereof that specifically bind human Dll4, in combination with one or more chemotherapeutic agents, and pharmaceutical compositions comprising a Dll4 antagonist and a chemotherapeutic agent.
2. Description of Related Art
Dll4 is a member of the Delta family of Notch ligands which exhibits highly selective expression by vascular endothelium (Shutter et al., 2000, Genes Develop. 14:1313-1318). Dll4 is a ligand for Notch receptors, including Notch 1 and Notch 4. Dll4 antagonists are useful for inhibiting tumor growth in various cancers. The nucleic acid and amino acid sequences for human Dll4 (hDll4) are shown in SEQ ID NOS:1 and 2, respectively. Antibodies specific for human Dll4 and cancer/tumor treatment using Dll4 antibodies are disclosed in international patent application publications WO 2007/143689, WO 2008/042236, and WO 2007/070671.
Chemotherapeutic agents are widely used for the treatment of cancer both alone and in combination with surgery and/or radiation therapy. Combination therapies using a Dll4 antagonist and chemotherapeutic agents are disclosed in US patent application publications US 2008/0014196 and US 2008/0107648.